TWI430813B - Vesicle composition, and external skin preparations - Google Patents

Description

Vesicle composition, and skin external preparation

The present invention relates to a vesicle composition using a lysophospholipid and an external preparation for skin formed from the vesicle-dispersed composition.

Since the vesicle has a closed cell which forms a two-molecular membrane structure of an amphoteric substance, the specific structure can contain an active ingredient and is attracting attention as a carrier of a drug delivery system (Drug Deliver System) or the like. Further, since the vesicle has high retention in the stratum corneum and the active ingredient acts efficiently, it is very effective as a skin external preparation.

There are many amphoteric substances that can form vesicles. In particular, vesicles formed by phospholipids are called liposome, and many reviews have been made on the safety surface of organisms. For example, phospholipid choline (Phosphatidyl Choline) has a purity of 90% or more, a phospholipid having an iodine value of 0.1 or less, and a liposome having a particle diameter of 100 to 150 nm (for example, refer to Patent Document 1). In addition, as a mixture of vesicles, a review of vesicles using synthetic surfactants has been conducted. A technique of using a vesicle preparation of maltitol difatty acid ester (for example, refer to Patent Document 2) or a technique of using a liposome of a multi-chain polyhydric-based surfactant (for example, refer to Patent Document 3).

On the other hand, a lysophospholipid-based hydrophilic surfactant is a technique using an emulsifier as an oil-in-water emulsion composition. For example, a cosmetic having a high transparency of a lysophospholipid, a phospholipid, and an oil is blended at a specific ratio (for example, refer to Patent Document 4). Further, a cosmetic for hair containing a phospholipid and a predetermined cationic surfactant is disclosed, and a lysosome can be used as a phospholipid (refer to Patent Document 5).

In addition, a liquid-based higher alcohol or a liquid higher fatty acid is used as a co-emulsifier which makes the emulsified particles finer (for example, refer to Patent Document 6).

In addition, an external preparation for skin such as a cosmetic is blended with an electrolyte for the purpose of imparting various cosmetic effects or added value. For example, an amino acid, an organic salt such as sodium dl-pyrrolidonecarboxylate, sodium lactate or an ascorbic acid derivative as a whitening component, or an inorganic salt such as sodium chloride.

[Patent Document 1] JP-A-2006-124378

[Patent Document 2] Japanese Patent Publication No. 06-157296

[Patent Document 3] JP-A-2006-290894

[Patent Document 4] JP-A-2001-302433

[Patent Document 5] JP-A-2006-193461

[Patent Document 6] JP-A-2004-277341

Although there are many techniques for such vesicle preparations, the following problems remain. For example, in the technique of Patent Document 1, although the feeling of use is excellent, it is odor-prone over time, or is limited by the pH range of the customizing agent, and the skin external preparation applied to cosmetics or the like is limited. According to the technique of Patent Document 2, compared with the liposome, the penetration to the skin is low and it feels sticky. Further, the technique of Patent Document 3 utilizes an amino acid-based surfactant, and although vesicles can be obtained by a simple method, the preservation stability is not sufficient. Further, in the presence of an electrolyte to which a moisturizing effect, a whitening effect, or the like is imparted, the actual situation is such that the technique destroys the bimolecular film structure unique to the vesicle, and the preservation property at high temperature is insufficient.

Therefore, it is required to develop an external preparation for skin which is excellent in the use of a liposome, which is different from the above-mentioned technique, and which forms a vesicle excellent in preservation stability, and further requires development of a storage stability of a vesicle even in the presence of an electrolyte. Excellent skin external preparation.

In the actual situation, the inventors of the present invention have found that lysophospholipids, one or two or more higher alcohols, liquid or higher fatty acids, cholesterol or phytosterols, which are liquid at 25 ° C, and The vesicles of purified water have excellent preservation stability, and the present invention has been completed.

The present invention provides a lysophospholipid which is usually used as a hydrophilic emulsifier, one or two or more kinds of higher alcohols, liquid or higher fatty acids, cholesterol or phytosterols selected from liquids at 25 ° C, and refined Water, novel and preserved vesicle composition with excellent stability.

That is, the present invention relates to the following components (a) to (d);

(a) Lysophospholipids

(b) one or more higher alcohols selected from the group consisting of higher alcohols or liquids at 25 ° C

(c) cholesterol or phytosterols

(d) a vesicle composition of purified water.

The present invention also relates to the above-described vesicle composition further comprising the component (e) electrolyte.

Further, the present invention also relates to the above-mentioned vesicle composition in which the component (b) and the component (c) have a mass ratio (b)/(c) of 0.2 to 4.

Further, the present invention also relates to the above-mentioned vesicle composition having a mass ratio (a)/[(b)+(c)] of the component (a), the component (b) and the component (c) of 0.25 to 5.

Further, in the present invention, the component (b) is one or more selected from the group consisting of oleyl alcohol, isostearyl alcohol, oleic acid, and isostearic acid.

Further, the present invention relates to the above-described vesicle composition characterized by having a conductivity of 0.02 to 2.5 s/m at 25 °C.

Further, from another viewpoint, according to the present invention, a skin external preparation containing the vesicle composition of any of the above is provided.

The vesicle composition of the present invention is excellent in storage stability. In addition, the vesicle composition of the present invention is effective as an external preparation for skin, because it has a high osmotic feeling to the skin, a feeling of not sticky, and further has a quality excellent in moisturizing effect.

[Best form for implementing the invention]

The invention is described in detail below. In addition, the numerical range represented by "-" in this specification is a range which has the numerical value of the lower-limit and upper-

The vesicle composition of the present invention contains (a) a lysophospholipid. (a) The lysophospholipid system is used as a vesicle composition structural component. There is no particular limitation on this type. Examples of the lysophospholipids include lysophospholipids derived from soybeans, hydrogenated lysophospholipids derived from soybeans, hydrolyzed phospholipids derived from egg yolk, hydrogenated lysophospholipids derived from egg yolk, and the like. These lysophospholipids may be used alone or in combination of two or more. (a) The lysophospholipid is an enzyme-modified phospholipid, and the ester bond at the 2-position is hydrolyzed by a phospholipase. The lysophospholipid used in the present invention has a hemolytic rate of lysophospholipid (the ratio of lysophospholipid in whole phospholipids) of 60% or more, and the purity of phospholipid choline (hereinafter referred to as "PC purity") is 20%. The above is appropriate. Since the lysophospholipid has one fatty acid chain, it has high hydrophilicity and chemical properties different from those of phospholipids compared with two phospholipids having a fatty acid chain.

The content of the component (a) lysophospholipid is not particularly limited, but is preferably 0.01 to 5% by mass (hereinafter simply referred to as "%"), and particularly preferably 0.05 to 3%. In this range, a vesicle composition having more excellent storage stability can be obtained.

In addition, lysophospholipids and phospholipids can also be used in combination.

The vesicle composition of the present invention contains (b) a higher alcohol or a liquid higher fatty acid which is liquid at 25 °C. The component (b) must be a vesicle structural component, and the crystallization of the component (c) can be suppressed, and the preservation stability can be improved. In addition, the component (b) contains a feeling of sensation of penetration to the skin or a feeling of not sticking to the skin, and is a vesicle composition which is particularly effective as a skin external preparation. Examples of higher alcohols which are liquid at 25 ° C, including octyldodecanol, oleyl alcohol, isostearyl alcohol, isocetyl alcohol, coconut alcohol, olive alcohol, jojoba alcohol, and mercaptotetradecane Alcohol; an example of a higher fatty acid which is liquid at 25 ° C, including isostearic acid, oleic acid, and linoleic acid. One or more of these may be used. Among them, oleyl alcohol, isostearyl alcohol, oleic acid, and isostearic acid are preferred.

The content of the component (b) is not particularly limited, but is preferably 0.01 to 5%, more preferably 0.05 to 3%. When it exists in this range, the vesicle composition which preserves stability is acquired.

The vesicle composition of the present invention contains (c) cholesterol or phytosterol. (c) Cholesterol or phytosterols help to form the stability of the bimolecular membrane structure when vesicles are formed, and this can improve storage stability.

The content of the component (c) is not particularly limited, but is preferably 0.01 to 5%, more preferably 0.05 to 3%. When it exists in this range, the vesicle composition which preserves stability is acquired.

In the vesicle composition of the present invention, when the mass ratio (b)/(c) of the component (b) to the component (c) is in the range of 0.2 to 4, the storage stability of the vesicle is further improved. If it is 0.5 to 2, the preservation stability will be further better. Further, in the vesicle composition of the present invention, the mass ratio (a) / [(b) + (c)] of the component (a), the component (b) and the component (c) is in the range of 0.25 to 5 The preservation stability of the vesicles will be even better. If it is in the range of 0.4 to 4, the preservation stability will be further better.

The vesicle composition of the present invention contains (d) purified water. (d) The purified water is an essential component of the skin external preparation containing vesicles as a dispersion medium of the components (a) to (c). The specific compounding amount can be appropriately determined depending on the contents of the components (a) to (c), and is about 50 to 99%.

The vesicle composition of the present invention becomes a bimolecular film in the component (d) by the balance of the hydrophilicity-lipophilicity of the hydrophilic component (a), the lipophilic component (b) and the component (c). structure. The lysophospholipids of the component (a) are as described above, and since they have high hydrophilicity as compared with the usual phospholipids, they are disadvantageous for the formation of vesicles. In the present invention, by using the component (a) lysophospholipid, component (b) liquid higher alcohol or liquid higher fatty acid, and component (c) cholesterol or phytosterol, this is supplemented to obtain hydrophilicity - A balance of lipophilicity provides a stable vesicle composition.

The vesicle composition of the present invention can be used as an external preparation for skin. This form is preferably more containing the component (e) electrolyte. (e) The electrolyte is blended to impart a moisturizing effect, an anti-inflammatory effect, a whitening effect, and the like.

Examples of the electrolyte having a moisturizing effect include organic compounds such as urea, or amino acid, lactic acid, citric acid, and pyrrolidone carboxylic acid, and metal salts such as potassium, sodium, magnesium, and calcium, sodium chloride, magnesium chloride, and the like. Inorganic salt.

Further, examples of the electrolyte having an anti-inflammatory effect include organic compounds such as glycyrrhizic acid and pantothenic acid, and metal salts such as potassium, sodium, magnesium, and calcium.

Further, examples of the electrolyte having whitening effect include ascorbic acid such as ascorbyl phosphate, ascorbyl alkyl ester, ascorbyl sulfate, ascorbyl glucoside, and the like, and metal salts such as sodium, potassium, magnesium, and calcium.

Further, for example, deep water of the ocean, hot spring water, or the like, a natural aqueous solution containing such an electrolyte or the like may be mentioned. These may be used in combination of one type or two or more types.

In the form of the skin external preparation, (e) the electrolyte is a water-soluble ascorbic acid derivative having a whitening effect, a lactate having a moisturizing effect, a pyrrolidone carboxylate or the like, and the like.

Further, specific examples of the electrolyte used for the external preparation for skin are described in the Western and Western Ages and other "Fragrance Journal" 1995-1 P.71-80; and "The Effectiveness of Cosmetics" Pharmaceutical Daily P.150.

The content of the component (e) is not particularly limited, but is preferably 0.01 to 10%, more preferably 0.1 to 5%. When it is in this range, the vesicle composition which is an external preparation for skin which is effective as a moisturizing effect, an anti-inflammatory effect, or a whitening effect can be obtained without impairing the preservation stability. The addition of the electrolyte usually causes the vesicles to be unstable, but since the vesicle composition of the present invention has high stability, it is maintained as a medicinal component such as a moisturizing effect, an anti-inflammatory effect, or a whitening effect, even if an electrolyte is added. Stability.

The vesicle composition of the present invention may contain various components in addition to the above-mentioned essential components (a) to (d). In particular, a polyhydric alcohol is contained, and a vesicle composition which is more excellent in preservation stability or use feeling can be obtained. The polyhydric alcohol is not particularly limited, but examples thereof include propylene glycol, 1,3-butylene glycol, dipropylene glycol, 1,2-pentanediol, glycerin, diglycerin, and sorbitol. Among them, 1,3-butanediol and dipropylene glycol are particularly preferred.

The conductivity of the vesicle composition of the present invention at 25 ° C (measured by using a conductivity meter CM-60G manufactured by Toa Denpa Kogyo Co., Ltd.) is preferably 0.02 to 2.5 s/m. It is especially preferable to be 0.05 to 2 s/m. In this range, the effect of the electrolyte (e), such as a moisturizing effect, an anti-inflammatory effect, or a whitening effect, can be sufficiently exerted without impairing the storage stability of the vesicles.

The vesicle composition of the present invention can be produced by various methods. This example is a solution in which the component (a) and the component (c) are dissolved in the component (b) at a temperature of about 80 ° C, and the component (d) having a temperature of about 80 ° C is stirred and mixed (the heating component is required ( e) A method of slowly cooling to room temperature after dissolution.

The present invention also relates to a skin external preparation containing a vesicle composition of the present invention. The external preparation for skin of the present invention may be added to any of the usual ingredients for external use of the skin, such as an oil agent, an alcohol, a powder, or a water-soluble substance other than the component (b), insofar as it does not impair the efficacy of the present invention. Molecules, film forming agents, surfactants, oil-soluble gelling agents, organically modified clay minerals, resins, ultraviolet absorbers, preservatives, antibacterial agents, perfumes, antioxidants, pH adjusters, chelating agents, and the like.

The use of the external preparation for skin of the present invention may, for example, be a skin care cosmetic such as lotion, lotion, cream, beauty lotion, massage material, facial mask, hand cream, body cream, or makeup primer. Further, the method of use may be, for example, a method of using a hand or a finger, a method of impregnating a nonwoven fabric, or the like.

[Examples]

The invention is illustrated in more detail below by way of examples, but the invention is not limited thereto.

[Example 1]

Inventive products 1 to 17 and comparative products 1 to 5: cosmetic liquid The vesicle composition of the composition shown in Tables 1 to 4 was prepared according to the following production method. It was confirmed that the vesicle formation was carried out under the observation of a polarizing microscope, and was judged by the amount of the Maltese Cross image.

In addition, the vesicle composition is applied to the skin as a cosmetic liquid, and the feeling of use and the moisturizing effect are evaluated. More specifically, the professional investigator performs a functional evaluation on (1) osmotic sensation, (2) presence or absence of stickiness, and (3) moisturizing effect. The combined results are shown in Tables 1 to 4.

(Production method)

A: The components (1) to (9) were heated to 80 °C.

B: The components (10) and (11) were dissolved by heating at 80 °C.

C: A was added to B, and the mixture was stirred and stirred by a disper mixer to form vesicles.

D: After cooling C to room temperature, components (12) and (13) were added to obtain a vesicle composition.

(Evaluation method: preservation stability of vesicles)

It was confirmed that the stability of the vesicles was carried out under a polarizing microscope. The state immediately after the preparation of the vesicle composition was compared with the state of the temperature at 40 ° C for 2 months. The amount of the Maltese cross image confirmed by the observation of time was determined using the following (i) four-stage determination criteria.

(i) 4-stage decision criteria

(Evaluation method: use feeling and moisturizing effect)

20 female investigators aged 20 to 40 years old used the prepared vesicle composition as a cosmetic liquid, and (1) osmotic feeling, (2) presence or absence of stickiness, and (3) moisturizing effect as a feeling of use, according to the following (ii) A 5-stage evaluation benchmark is used to perform a functional assessment, and an average of the total investigator's score is determined based on the (iii) 4-stage decision criteria.

(ii) 5-stage evaluation benchmark

(iii) 4-stage decision criteria

(Evaluation method: conductivity)

The conductivity of each sample at 25 ° C was measured using a conductivity meter (conductivity meter CM-60G manufactured by Toa Dentsu Kogyo Co., Ltd.).

From the results of Tables 1 to 4, it was revealed that the inventive products 1 to 17 were excellent in stability at a constant temperature of 40 ° C for two months. In addition, when applied to the skin as a beauty liquid, it is excellent in a feeling of penetration, a feeling of use which is not sticky, and an excellent moisturizing effect.

On the other hand, the comparative product 1 which does not contain the component (a) has not formed vesicles. Further, the comparative products 2 and 3 which do not contain the component (b) and the component (c), the comparative product 4 which contains stearyl alcohol in place of the component (c), and the comparative product 5 which contains a phospholipid instead of the component (a) When vesicles were formed, any one of them was observed over time, and it was observed that there was a problem in preservation stability of crystal precipitation or precipitation of cholesterol.

[Example 2: lotion]

(Note 3) The hemolytic rate was 68%, and the PC purity was 30%.

(method of law)

A: The components (1) to (5) were dissolved by heating at 80 °C.

B: The component (6) was heated to 80 °C.

C: A was added to B, and under agitation, vesicles were formed and cooled to room temperature.

D: Adding ingredients (7) to (12) to C to obtain a lotion.

The lotion-based vesicles of Example 2 have excellent storage stability, excellent skin penetration, and are not sticky, and have a moisturizing effect. In addition, the conductivity was 0.05 s/m.

[Example 3: Oil-in-water emulsion]

(Note 4) Pemulen TR-2 (made by NOVEON)

(Note 5) The hemolytic rate is 88%, and the PC purity is 80%.

(Production method)

A: The dissolved components (1) to (7) were heated to 70 °C.

B: After heating the components (8) to (12) to 70 ° C, they were added to A to carry out emulsification.

C: B was cooled to room temperature.

D: The components (14) to (18) were dissolved by heating at 80 °C.

E: The component (19) was heated to 80 ° C, and D was added thereto, followed by mixing and stirring to form vesicles.

F: After cooling E, it is added to C, and component (13) is further added to obtain an oily emulsion in water.

The oil-in-water emulsion type vesicles of Example 3 have excellent storage stability, excellent osmotic feeling, and are excellent in skin external preparations which are not sticky and have a moisturizing effect. In addition, the conductivity was 0.02 s/m.

[Example 4: Oil-type cream in water]

(method of law)

A: The components (1) to (6) were dissolved by heating at 70 °C.

B: The components (7) and (8) were dissolved by heating at 70 ° C, and then added to A to carry out emulsification.

C: After cooling B to room temperature, components (9) to (11) were added.

D: The components (12) to (15) were dissolved by heating at 80 °C.

E: The component (16) was heated to 80 ° C, and D was added thereto, followed by mixing and stirring to form vesicles.

F: After cooling E, it is added to C to obtain a cream.

The oil-in-water cream vesicle of Example 4 is excellent in preservation stability, excellent in osmotic feeling, and non-tacky and moisturizing effect. In addition, the conductivity was 0.07 s/m.

[Example 5: Flaky cosmetic]

(method of law)

A: The components (1) to (7) were dissolved by heating at 80 °C.

B: The component (8) was heated to 80 ° C, and A was added thereto, followed by mixing and stirring to form vesicles.

C: After cooling B, components (9) to (14) were added and impregnated into the nonwoven fabric.

D: The C-sealing was filled in an aluminum laminated bag-shaped container to obtain a sheet-like cosmetic.

The flaky crude material vesicles of Example 5 are excellent in storage stability, excellent in osmotic feeling, and non-tacky and moisturizing effect. In addition, the conductivity was 1.18 s/m.

[Example 6: Oil-based creamy base primer]

(Note 6) KP-543 (propylene-polyoxyalkylene graft copolymer 50%: 50% butyl acetate mixture, manufactured by Shin-Etsu Chemical Co., Ltd.)

(Production method)

A: The components (1) to (5) were dispersed and treated in a 3-roll mixer.

B: The components (6) to (11) were uniformly mixed.

C: Added to A at B for emulsification.

D: The components (12) to (15) were dissolved by heating at 80 °C.

E: The component (16) was heated to 80 ° C, and D was added thereto, followed by mixing and stirring to form vesicles.

F: After cooling E, it is added to C to obtain an oily creamy base primer in water.

The oil-in-water cream-like primer liquid of Example 6 is a skin external preparation which is excellent in storage stability, excellent in osmotic feeling, and which is not sticky and has a moisturizing effect. In addition, the conductivity was 0.13 s/m.

Claims (7)

A vesicle composition comprising the following components (a) to (d); (a) lysophospholipid (b), one or more selected from the group consisting of higher alcohols or liquids at 25 ° C in liquid form Higher fatty acid (c) cholesterol or phytosterol (d) purified water, wherein the content of the component (a) is 0.01 to 5% by mass, and the oil content of the component (b) is 0.01 to 5% by mass, and the component (c) The oil content is 0.01 to 5% by mass, and the mass ratio (b)/(c) of the component (b) to the component (c) is 0.2 to 4, and the components (a), the components (b), and the component (c) are contained. The mass ratio (a)/[(b)+(c)] is 0.25~5. A vesicle composition according to claim 1 which further comprises a polyhydric alcohol selected from the group consisting of 1,3-butanediol and dipropylene glycol. The vesicle composition according to claim 1, wherein the component (b) is one or more selected from the group consisting of higher alcohols which are liquid at 25 ° C. The vesicle composition according to any one of claims 1 to 3, which further comprises the component (e) electrolyte. The vesicle composition of the first aspect of the invention, wherein the component (b) is one or more selected from the group consisting of oleyl alcohol, isostearyl alcohol, oleic acid, and isostearic acid. Such as the vesicles of any one of claims 1 to 3 The composition has a conductivity of 0.02 to 2.5 s/m at 25 °C. A skin external preparation characterized by comprising the vesicle composition according to any one of claims 1 to 3.